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Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans

Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous...

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Autores principales: Byun, Kyunghee, Bayarsaikhan, Delger, Bayarsaikhan, Enkhjargal, Son, Myeongjoo, Oh, Seyeon, Lee, Jaesuk, Son, Hye-in, Won, Moo-Ho, Kim, Seung U., Song, Byoung-Joon, Lee, Bonghee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139297/
https://www.ncbi.nlm.nih.gov/pubmed/25140518
http://dx.doi.org/10.1371/journal.pone.0104699
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author Byun, Kyunghee
Bayarsaikhan, Delger
Bayarsaikhan, Enkhjargal
Son, Myeongjoo
Oh, Seyeon
Lee, Jaesuk
Son, Hye-in
Won, Moo-Ho
Kim, Seung U.
Song, Byoung-Joon
Lee, Bonghee
author_facet Byun, Kyunghee
Bayarsaikhan, Delger
Bayarsaikhan, Enkhjargal
Son, Myeongjoo
Oh, Seyeon
Lee, Jaesuk
Son, Hye-in
Won, Moo-Ho
Kim, Seung U.
Song, Byoung-Joon
Lee, Bonghee
author_sort Byun, Kyunghee
collection PubMed
description Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE-albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration.
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spelling pubmed-41392972014-08-25 Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans Byun, Kyunghee Bayarsaikhan, Delger Bayarsaikhan, Enkhjargal Son, Myeongjoo Oh, Seyeon Lee, Jaesuk Son, Hye-in Won, Moo-Ho Kim, Seung U. Song, Byoung-Joon Lee, Bonghee PLoS One Research Article Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE-albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration. Public Library of Science 2014-08-20 /pmc/articles/PMC4139297/ /pubmed/25140518 http://dx.doi.org/10.1371/journal.pone.0104699 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Byun, Kyunghee
Bayarsaikhan, Delger
Bayarsaikhan, Enkhjargal
Son, Myeongjoo
Oh, Seyeon
Lee, Jaesuk
Son, Hye-in
Won, Moo-Ho
Kim, Seung U.
Song, Byoung-Joon
Lee, Bonghee
Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans
title Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans
title_full Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans
title_fullStr Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans
title_full_unstemmed Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans
title_short Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans
title_sort microglial age-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139297/
https://www.ncbi.nlm.nih.gov/pubmed/25140518
http://dx.doi.org/10.1371/journal.pone.0104699
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